# Impact of the C. difficile small acid soluble proteins on spore physiology

> **NIH NIH R01** · TEXAS A&M UNIVERSITY · 2022 · $573,425

## Abstract

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea in the hospital and
long term health care settings. In addition to the patient toll, the treatment-associated costs of
C. difficile infections to the United States healthcare system have been estimated at $5 billion.
Although the rate of C. difficile infection in the United States is rising, surprisingly little is known
about the mechanisms by which C. difficile spores maintain their extreme resistance properties.
C. difficile is believed to be acquired by the host in the form of a dormant spore which
contaminates the nosocomial environment. In other organisms, a significant amount of resistant
to UV and genotoxic chemicals is provided by the small acid soluble proteins (SASPs). SASPs
are thought to nonspecifically bind to DNA and alter its form to prevent the formation of
thymidyl-thymidine adducts (thymidine dimers) upon UV exposure. These proteins also provide
resistances to reactive oxygen, acids, crosslinking agents and minor resistance to heat. In C.
difficile, however, nothing is known about how these important proteins contribute to the C.
difficile spore resistance spectrum. C. difficile SspA provides resistance to UV but SspA & SspB
play a role in spore formation. The C. difficile ΔsspA ΔsspB double mutant strain does not
produce mature spores suggesting that these SASPs regulate, at some level, the sporulation
program. This application will analyze the impact of SASPs on spore biology in three aims. Aim
1 investigates how SspA & SspB contributes to spore formation and how the C. difficile SASPs
protect the C. difficile genome from UV damage. Aim 2 investigates mechanisms by which the
SASPs contribute to spore formation. Aim 3 investigates how the protease that degrades the
SASPs during germination is regulated and its spectrum of activity in the spore. Successful
completion of these aims will thoroughly characterize the impact of SASPs on spore resistance
and lead to the future design of agents that can clean a contaminated environment.

## Key facts

- **NIH application ID:** 10533031
- **Project number:** 1R01AI172043-01
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Joe Sorg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $573,425
- **Award type:** 1
- **Project period:** 2022-08-08 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10533031

## Citation

> US National Institutes of Health, RePORTER application 10533031, Impact of the C. difficile small acid soluble proteins on spore physiology (1R01AI172043-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10533031. Licensed CC0.

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